The natural history of diabetic retinopathy is extremely variable among individual diabetic patients. At the present time no method is available that is able to predict which diabetics will develop the more advanced forms of retinopathy with their attendant poor visual prognosis. There is evidence that genetic factors, in addition to the metabolic abnormalities of diabetes, are important in the pathogenesis of diabetic retinopathy. The hypothesis for the proposed study is that there are one or more "microangiopathy genes" in linkage disequalibrium with the HLA genes which determine susceptibility to serve diabetic microangiopathy. We plan to test this hypothesis by studying HLA A,B,C and D antigens and B-cell alloantigens in JIDD patients with and without severe retinopathy to see if differences exist. Similar studies will be carried out in AOD patients with and without advanced retinopathy. Prospective studies will be completed in patients followed in the DRS and ETDRS at the University of Minnesota. In addition to these association studies, linkage studies will be carried out in large diabetic multiplex families selected for either a high or low prevalence of proliferative retinopathy. The determination of genetic markers for microangiopathy, which could serve as predictors for vascular complications, would have great practical significance for all patients with diabetes mellitus.